Heparanase and its uses related to exostoses

Abstract

Methods of treating or preventing exostosis in a subject comprising administering to a subject with exostosis or at risk of developing exostosis an effective amount of an agent that that cleaves heparan sulfate or an agent that increases expression of an enzyme that cleaves heparan sulfate are provided herein.

1 . A method of treating or preventing exostosis in a subject, comprising administering to a subject with exostosis or at risk of developing exostosis an effective amount of an agent that cleaves heparan sulfate. 
     
     
         2 . The method of  claim 1 , wherein the agent is a heparanase. 
     
     
         3 . A method of treating or preventing an osteochondroma-related disease in a subject, comprising administering to a subject with or at risk of developing an osteochondroma-related condition, an effective amount of an agent that cleaves heparan sulfate. 
     
     
         4 . The method of  claim 3 , wherein the agent is a heparanase. 
     
     
         5 . The method of  claim 3 , wherein the disease is multiple hereditary exostoses (MHE). 
     
     
         6 . A method of treating or preventing exostosis in a subject, comprising administering to a subject with exostosis or at risk of developing exostosis an effective amount of an agent that increases expression of an enzyme that cleaves heparan sulfate in the subject. 
     
     
         7 . The method of  claim 6 , wherein the enzyme is a heparanase. 
     
     
         8 . A method of treating or preventing an osteochondroma-related disease in a subject, comprising administering to a subject with or at risk of developing an osteochondroma-related condition, an effective amount of an agent that increases expression of an enzyme that cleaves heparan sulfate in the subject. 
     
     
         9 . The method of  claim 8 , wherein the enzyme is a heparanase. 
     
     
         10 . The method of  claim 7 , wherein the disease is multiple hereditary exostoses (MHE). 
     
     
         11 . A method of identifying an agent that treats or prevents exostosis in a subject comprising contacting a transgenic animal comprising a functional deletion of one or both Ext1 alleles with a test agent, wherein if the test agent decreases or prevents exostosis in the animal, the test agent is an agent that treats or prevents exostosis in a subject. 
     
     
         12 . The method of  claim 11 , wherein both Ext1 alleles are functionally deleted. 
     
     
         13 . The method of  claim 11 , wherein the transgenic animal comprises a tamoxifen-inducible Cre transgene (Cre-ERT2) under the control of the Colalpha(II) promoter. and a transgene comprising loxP flanked Ext1 alleles.